Coexistence of submandibular epithelioid angiosarcoma and papillary thyroid carcinoma: A case report.

INTRODUCTION: Reports on the coexistence of epithelioid angiosarcoma (EA) and papillary thyroid carcinoma (PTC) are rare. Over the past 50 years, only 2 cases of coexistence of EA and PTC have been reported in English literature. Therefore, we report a rare case of coexistence of EA and PTC treated with surgery and adjuvant radiation therapy. PATIENT CONCERNS: A 64-year-old man visited our hospital with a painless mass in the left submandibular gland, with poor mobility. DIAGNOSIS: Neck ultrasonography revealed nodules in the left submandibular gland and multiple cystic-solid mixed nodules in the left thyroid gland. Pathological findings revealed coexistence of EA in the left submandibular gland area and PTC in the left thyroid gland. INTERVENTIONS: The patient underwent resection of the left submandibular gland, deep maxillofacial tumor, total thyroidectomy, left neck I, II, III, and VI regional lymph node dissection, and recurrent laryngeal nerve exploration under general anesthesia. Two months postoperatively, the patient also received adjuvant radiation therapy in the local and adjacent areas, with 4MV-X IMRT DT50GY at 2Gy/day 25 fractions. OUTCOMES: The follow-up period was 37 months. The patient recovered well without focal neurological deficits, local recurrence, or distant metastasis after surgery, except for grade I skin reaction after adjuvant radiation therapy. CONCLUSIONS: This is a rare case report of the coexistence of EA in the left submandibular gland and PTC in the left thyroid gland. Although multiple examinations were used, precise preoperative diagnosis was challenging owing to the coexistence of EA and PTC. Surgery and radiotherapy were effective treatments for the coexistence of EA and PTC in this case.

Promoting the formation of Pi-stacking interaction to improve CTL cells activation between modified peptide and HLA.

OBJECTIVE: This study aims to investigate the use of single residue substitution to promote the formation of pi-stacking interactions between peptides and Human leukocyte antigen (HLA)-A*2402 molecules to improve the affinity of peptides and HLA molecules, as well as the level of cytotoxic T lymphocyte (CTL) cells activated by peptides-HLA (p-HLA) complex. METHODS: Molecular docking and molecular dynamics simulation were used to simulate and analyze the interactions and binding free energies between HLA-A*2402-restricted antigen peptides and HLA molecules, before and after the single residue substitution. HLA-A*2402 restricted antigen peptides before and after the single residue replacement were loaded into dendritic cells (DCs) in vitro, and further Enzyme-Linked ImmunoSpot (ELispot) test was carried out to evaluate the effect of modified antigen peptides on the immune activation of CTL cells. RESULT: After replacing the antigen peptides with a single residue, some of them could promote the formation of pi-stacking interaction. The binding free energy between the modified antigen peptides and HLA-A*2402, as well as the level of immune activation of CTL cells were mostly higher than before, especially after the replacement of the 9th residue of the polypeptide, such as C9F and C9W. There was a significant negative correlation between the level of activated CTL cells by modified antigen peptides and the total interaction amount of hydrogen bonds and salt bridges. CONCLUSION: Promoting the formation of pi-stacking interaction between antigen peptides and HLA-A*2402 molecules could increase the total binding free energy of p-HLA complex and the level of CTL cells activation. In addition, the amount of hydrogen bonds and salt bridges between peptides and HLA could reduce the level of immune activation. All the characteristics above can improve the immunogenicities of the weak antigens.

The Role, Function, and Mechanism of Long Intergenic Noncoding RNA1184 (linc01184) in Colorectal Cancer.

BACKGROUND: Long intergenic noncoding RNA1184 (linc01184) has been recently discovered; however, its role in human diseases is limited to date. The present study is aimed at investigating the expression pattern and mechanism of linc01184 in colorectal cancer (CRC) tumorigenesis. METHODS: The expression of linc01184 in CRC tissues and cell lines was compared with that in normal controls. The functions of linc01184 in CRC cells were identified by overexpression and small interfering RNA (siRNA) approaches in vitro. Meanwhile, the target gene prediction software, luciferase reporter, RNA pull-down, and western blotting assays were used to analyze the oncogenic mechanism. RESULTS: We found that linc01184 was obviously upregulated in CRC tissues and cells when compared to normal controls, and its upregulation had a positive association with the CRC progression. linc01184 knockdown significantly suppressed CRC cell proliferation and invasion and promoted apoptosis. Besides, linc01184 acted as a competitive endogenous RNA (ceRNA) by directly binding to microRNA-331 (miR-331), and its overexpression resulted in notable increases of human epidermal growth factor receptor 2 (HER2), phosphorylated Ser/Thr kinases (p-Akt), and extracellular regulated protein kinase 1/2 (p-ERK1/2) at posttranscriptional levels in CRC cells, which were antagonized by miR-331. CONCLUSIONS: The findings reveal for the first time that linc01184 is an enhancer for the proliferation and invasion of CRC by functioning as a ceRNA through the linc01184-miR-331-HER2-p-Akt/ERK1/2 pathway regulatory network.

Palliative whole-brain radiotherapy and health- related quality of life for patients with brain metastasis in cancer.

OBJECTIVE: To assess the use of palliative whole-brain radiotherapy (WBRT) in the treatment of brain metastases (BMs) and to evaluate the health-related quality of life (HRQOL) of these patients. MATERIALS AND METHODS: We conducted a retrospective study of 46 patients with BMs who were treated with WBRT at the First Affiliated Hospital of Xi'an Jiaotong University between January 2013 and January 2015. External beam radiotherapy techniques were used to deliver 40 Gy in 20 fractions or 30 Gy in ten fractions with a 10 MV photon beam from a linear accelerator to the whole brain. Data were stored and analyzed using SPSS version 17.0. RESULTS: Of the 46 patients, the survival time of patients in our study was 10.8±0.55 months: 11.8±0.46 months in patients with WBRT, 11.75±1.00 in patients with WBRT + chemotherapy, and 3±0.79 months in patients with supportive care, respectively (P<0.01). The HRQOL scores of all the patients were 70±1.16 (before therapy) and 76.83±1.04 (after therapy) (P<0.01). The HRQOL scores of the patients with WBRT were 72.23±0.88 (before therapy) and 78.49±0.87 (after therapy) (P<0.01). There was no central nervous system toxicity; only two (4.3%) patients were found to have BM hemorrhage. Radiation necrosis happened in one patient (2.2%). CONCLUSION: Effective treatment options for patients with BMs are important. WBRT was evaluated to ensure survival outcomes and QOL were enhanced after therapy for patients with BMs.

Sphingosine kinase 1 as an anticancer therapeutic target.

The development of chemotherapeutic resistance is a major challenge in oncology. Elevated sphingosine kinase 1 (SK1) levels is predictive of a poor prognosis, and SK1 overexpression may confer resistance to chemotherapeutics. The SK/sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor (S1PR) signaling pathway has been implicated in the progression of various cancers and in chemotherapeutic drug resistance. Therefore, SK1 may represent an important target for cancer therapy. Targeting the SK/S1P/S1PR signaling pathway may be an effective anticancer therapeutic strategy, particularly in the context of overcoming drug resistance. This review summarizes our current understanding of the role of SK/S1P/S1PR signaling in cancer and development of SK1 inhibitors.

Analysis of the characteristics and prognosis of advanced non-small-cell lung cancer in older patients.

OBJECTIVE: Lung cancer is still the leading cause of cancer-related deaths worldwide. However, most elderly patients with advanced non-small-cell lung cancer (NSCLC) have been undertreated and the outcome related to age is controversial. A retrospective analysis was conducted for advanced NSCLC in order to investigate the characteristics and prognosis of older patients. METHODS: Medical records were collected from 165 patients with NSCLC (stages IIIA-IIIB) who had been treated with concurrent chemoradiotherapy (CRT) or radiotherapy from January 2009 to January 2011. The cases were divided into two age groups 1) patients ≥70 years old; 2) patients <70 years old. There were 73 patients in group I, 92 in group II. Patient characteristics, treatment toxicities, and prognosis were evaluated. RESULTS: Of the 165 patients analyzed, 34 patients (34/73) in group I received concurrent CRT while 47 (47/92) in group II completed that treatment. No significant difference was observed in the reason for patients who discontinued CRT in two groups (P>0.05). In the patients with adenocarcinoma, more cases were found in group II than that in group I; the more squamous cell carcinoma and the more smokers with squamous cell carcinoma were seen in older group (P<0.05). With a median follow-up of 20.5 months, the 1-year survival for group I and II were 49.3% and 40.2% respectively (P=0.243). Two-year survival for the two groups was 20.5% and 16.3% (P=0.483); 3-year survival was 9.6% and 9.8% (P=0.967). There was no significant difference between two groups statistically in survival by univariate analysis (P>0.05). The therapy-related toxicities in group I seem to be similar to the group II (P>0.05). CONCLUSION: More adenocarcinoma patients were found in youthful lung cancer and the more smokers with squamous cell carcinoma were seen in older group. Age is not the important factor for the selection and allocation of treatment in advanced NSCLC. The same prognosis and toxicities had been shown in older and young. Age may not be an independent increased risk of death in advanced NSCLC.

[Construction of a new vector for direct cloning of PCR products].

A new method for construction of a cloning vector (T-vector) for direct ligation with PCR products was described. The T-vector derived from pUC118 in which the unique restriction site of Eam1105 I in the region of Amp(r) gene was deleted and an artificial DNA fragment flanking two Eam1105 I was introduced at the site of BamHI. The modified vector was named as pUC118E. A T-vector with 3' over hang end of a single T can be obtained via digesting of pUC118E with Eam1105I. PCR products can be easily cloned with this T-vector.

RNAi-mediated ERBB2 gene knockdown sensitizes human colorectal cancer cells to radiation.

This study aimed to investigate the involvement of c-erbB-2, encoded by the receptor tyrosine kinase ERBB2 gene, in the pathogenesis of colorectal cancer and to validate its potential as an anticancer target. Immunohistochemical and histopathological analyses were applied in tissue samples derived from 80 colorectal cancer patients. ERBB2 stable small hairpin RNA (shRNA) knockdown in HT29 human colorectal cancer cells was confirmed by RT-PCR and western blotting. Cell cycle profile and apoptosis were measured using PI or Annexin V-PI dual staining. A significant correlation between ERBB2 levels and Dukes' stage of colorectal cancer, in both the primary malignancy and lymph node metastatic tissues, was observed. ERBB2-depleted HT-29 cells exhibited increased sensitivity to radiation compared to control cells, likely due to enhanced G0/G1 phase cell cycle arrest and apoptosis. ERBB2 may be involved in the malignancy and metastasis of colorectal cancer. Overexpressed ERBB2 may constitute a potential target for colorectal cancer therapy.

[Biological behaviour of colon cancer cells transfected with C-erbB2 shRNA plasmid].

AIM: To study the changes of the cell growth, cell cycle distribution and cell apoptosis of colon cancer cell, HT-29, when C-erbB2 gene was knockdown by shRNA against C-erbB2. METHODS: Cell growth, cell cycle distribution and cell apoptosis were compared among three groups including plasmid experimental group(PEG), transfected reagent control group(TRCG)and negative plasmid control group(NPCG). Cell growth was measured by MTT assay. Cell cycle distribution and cell apoptosis were detected by flow cytometry. RESULTS: The inhibition rate of cell growth of PEG, TRCG and NPCG were 39.65%, 7.23% and 8.05% respectively. The cell growth was significantly inhibited in PEG(P<0.01). The cells of G0/G1 phase were 74.93%, 67.19%, 68.05% respectively in PEG, TRCG and NPCG. The cells of G0/G1 phase in PEG were significantly more than those in TRCG and NPCG(P<0.05).While the cells of S phase were 7.81%, 14.02%, 13.70% in PEG, TRCG and NPCG respectively. The cells of S phase in PEG were significantly less than those in TRCG or NPCG(P<0.05).The cell apoptosis rate were 19.21%, 3.13%, 4.08% in PEG, TRCG and NPCG respectively. The cell apoptosis rate in PEG was significantly higher than those in TRCG or NPCG(P<0.01). CONCLUSION: Cell growth was inhibited by shRNA against C-erbB2 gene. Cell cycle was blocked in G0/G1 phase and apoptosis was induced by C-erbB2 shRNA. This indicates C-erbB2 gene plays important roles in the carcinogenesis and development of colon cancer.

[Construction and identification of CerbB-2 siRNA expression plasmid and its transfer into human colon cancer cell lines HT-29].

OBJECTIVE: To construct a plasmid carrying small interfering RNA (siRNA) targeting human C-erbB2 gene (pGenesil- erbB2) and test its effect on Her-2 expression at the post-transcriptional level in human colon cancer cell lines HT-29 cells that highly express erbB2. METHODS: A HT-29 cell line that highly expressed CerbB-2 was selected using immunohistochemical method. The double-stranded siRNA targeting human CerbB-2 cDNA and the negative control fragment were cloned into pGenesil-1 vector, and after identification and sequence analysis, the constructed pGenesil-erbB2 plasmid was transfected into the selected HT-29 cell line. RESULTS: The pGenesil-erbB2 plasmid was successfully constructed and stably transferred into HT-29 cells. The transfection resulted in significant inhibition of Her-2 protein expression in the HT-29 cells, as shown by Western blotting. CONCLUSION: The pGenesil-erbB plasmid we constructed can be stably transfected into HT-29 cells to inhibit the expression of Her-2 protein, and can be useful in further studies of increasing the radiosensitivity of HT-29 cell lines.